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Akt/Protein Kinase B Is Required for Lymphatic Network Formation, Remodeling, and Valve Development.

Zhou, Fei and Chang, Zai and Zhang, Luqing and Hong, Young-Kwon and Shen, Bin and Wang, Bo and Zhang, Fan and Lu, Guangming and Tvorogov, Denis and Alitalo, Kari and Hemmings, Brian Arthur and Yang, Zhongzhou and He, Yulong (2010) Akt/Protein Kinase B Is Required for Lymphatic Network Formation, Remodeling, and Valve Development. The American Journal of Pathology. ISSN 0002-9440

Abstract

Akt-mediated signaling plays an important role in blood vascular development. In this study, we investigated the role of Akt in lymphatic growth using Akt-deficient mice. First, we found that lymphangiogenesis occurred in Akt1(-/-), Akt2(-/-), and Akt3(-/-) mice. However, both the diameter and endothelial cell number of lymphatic capillaries were significantly less in Akt1(-/-) mice than in wild-type control mice, whereas there was only a slight change in Akt2(-/-) and Akt3(-/-) mice. Second, valves present in the small collecting lymphatics in the superficial dermal layer of the ear skin were rarely observed in Akt1(-/-) mice, although these valves could be detected in the large collecting lymphatics in the deep layer of the skin tissues. A fluorescence microlymphangiography assay showed that the skin lymphatic network in Akt1(-/-) mice was functional but abnormal as shown by fluorescein isothiocyanate-dextran draining. There was an uncharacteristic enlargement of collecting lymphatic vessels, and further analysis showed that smooth muscle cell coverage of collecting lymphatic vessels became much more sparse in Akt1-deficient mice than in wild-type control animals. Finally, we showed that lymphatic vessels were detected in compound Akt-null mice and that lymphangiogenesis could be induced by vascular endothelial growth factor-C delivered via adenoviral vectors in adult mice lacking Akt1. These results indicate that despite the compensatory roles of other Akt isoforms, Akt1 is more critically required during lymphatic development.

Item Type: Article
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Date Deposited: 11 Oct 2010 23:45
Last Modified: 01 Feb 2013 00:48
URI: https://oak.novartis.com/id/eprint/3757

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